A Male Contraceptive Pill: Progress, Challenges and Future Directions

The concept of a male contraceptive pill has long been pursued as a way to balance contraceptive responsibility between men and women. While multiple female oral contraceptives have been available since the 1960s, men have historically had limited options: condoms or vasectomy. The development of an oral contraceptive for men has the potential to transform reproductive health, providing a reversible, daily method of birth control.

Male contraceptive pills aim to regulate hormone levels in a way that suppresses sperm production without causing severe side effects. One promising candidate, dimethandrolone undecanoate (DMAU), has advanced through early-phase trials and has demonstrated both safety and hormonal effects consistent with contraception. Ongoing research continues to explore hormonal and non-hormonal strategies to create a viable daily pill for men.

How male contraceptive pills work

Hormonal regulation of male fertility

Spermatogenesis – the production of sperm – is regulated by the hypothalamic-pituitary-gonadal axis. Gonadotropin-releasing hormone from the hypothalamus stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH acts on Leydig cells to produce testosterone, while FSH supports Sertoli cells in sperm development. Suppressing LH and FSH reduces sperm output, which is one of the primary targets of hormonal male contraceptives.

The role of androgens and progestins

Experimental male pills often combine an androgen, such as testosterone or a synthetic derivative, with a progestin. This combination suppresses endogenous testosterone production and spermatogenesis while maintaining enough circulating androgen to preserve secondary sexual characteristics and libido. DMAU integrates these effects into a single molecule with androgenic and progestogenic activity.

Clinical trial results: DMAU

A key study investigated DMAU in 100 healthy men aged 18 to 50. Participants received one of three doses –100, 200, or 400 mg – of DMAU or placebo for 28 days. The compound was delivered in different formulations, including castor oil and powder, to evaluate absorption.

The trial revealed that at the highest tested dose of 400 mg, DMAU significantly suppressed testosterone, LH and FSH to levels consistent with effective contraception. Importantly, this suppression was achieved with minimal symptoms of testosterone deficiency, despite low circulating testosterone levels. Lead investigator Dr. Stephanie Page described DMAU as "a major step forward in the development of a once-daily male pill," emphasizing that many men prefer a pill over injections or topical gels.

Safety assessments showed that DMAU was well tolerated. Mild side effects included modest weight gain and reduced HDL cholesterol. Crucially, no markers of liver or kidney dysfunction were observed, addressing one of the major limitations of earlier oral androgen formulations, which cleared too quickly or induced liver toxicity.

Barriers to male birth control development

Traditional testosterone-based therapies clear rapidly from the body, requiring multiple daily doses and creating challenges for consistent hormonal suppression. Additionally, oral testosterone can exert hepatotoxic effects. DMAU addresses these limitations by incorporating an undecanoate ester, which slows clearance and allows once-daily dosing when taken with food.

Developing a male contraceptive pill is not only a pharmacological challenge but also a behavioral one. Studies indicate that many men express willingness to use an oral contraceptive, yet societal perceptions and partner acceptance remain critical factors. The ease of use offered by a daily pill could increase adherence compared with longer-acting injections or implants.

Alternative strategies in male contraception

The range of current approaches to male contraception under investigation can be grouped as follows:

• Hormonal approaches: Beyond DMAU, other androgen-progestin combinations such as testosterone undecanoate paired with various progestins, delivered via injectable or transdermal systems.
• Non-hormonal compounds: Small molecules like YCT529 that target the retinoic acid receptor-alpha, showing high contraceptive efficacy in animal studies.
• Polymer-based interventions: Approaches such as Reversible Inhibition of Sperm Under Guidance (RISUG™), which blocks sperm passage, and Vasalgel™, a long-acting, reversible alternative to vasectomy.

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Implications for reproductive health

The development of a male contraceptive pill represents a paradigm shift in family planning. Shared contraceptive responsibility could improve gender equity in reproductive health. Moreover, reversible oral options would expand the contraceptive toolbox beyond condoms and vasectomy, potentially reducing unintended pregnancies worldwide.

From a laboratory perspective, progress in male contraception illustrates the integration of endocrinology, pharmacology and drug formulation science. For researchers, the challenge lies not only in developing effective suppression of spermatogenesis but also in ensuring safety, tolerability and reversibility.

Longer-term studies are underway to confirm whether DMAU and similar compounds can consistently suppress sperm production without long-term adverse effects. Researchers are also investigating novel molecular targets for non-hormonal contraception, broadening the potential for innovation.

The path toward a male pill mirrors the trajectory of female contraceptives, which took decades of refinement before achieving widespread acceptance. As male contraceptive research matures, laboratory discoveries will play a central role in shaping a new era of reproductive medicine.

This article is a rework of a press release issued by the Endocrine Society. Material has been edited for length and the content has been updated to provide additional context and details of related developments since the original press release was published on our website. This content includes text that has been created with the assistance of generative AI and has undergone editorial review before publishing. Technology Networks' AI policy can be found here.